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 Saturday, 19 April 2003 05:30 PM GMT

 

Both CDC & WHO have received reports of outbreaks of a severe form of pneumonia worldwide.

 
 

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Infectious disease review
First there was SARS, now there's West Nile Virus.

 
   
 
     

In March 2003 the WHO and U.S. Centers for Disease Control and Prevention issued a global alert over cases of atypical pneumonia that do not appear to respond to treatment. This happened after outbreaks have occurred in several counties over the past month. Countries include Canada, China, Hong Kong Special Administrative Region of China, Indonesia, Singapore, Thailand, and Viet Nam.

SARS or Severe Acute Respiratory Syndrome is a form of lung injury characterized by increased permeability of the alveolar-capillary membrane, diffuse alveolar damage, and the accumulation of proteinaceous pulmonary edema and rapidly leads to pulmonary failure.

Cause

Just last month it was not known if this disease is caused by a virus or a bacteria. Now it has been established that the SARS virus is a new coronavirus unlike any other known human or animal virus in the Coronavirus family. Because the virus is new, much about its behaviour is poorly understood.

Spread

Spread seems to be person-to-person, with a number of cases in Asia being reported among health care and other hospital workers, as well as household contacts of the patients.

That pattern of transmission is typical of any flu-like illness. The average incubation period between exposure to a sick person and onset of symptoms is about three days. The CDC put the incubation period at between two and seven days.

As of today (19th of April, 2003), a cumulative total of 3547 cases with 182 deaths have been reported from 25 countries. Compared with yesterday, 12 new deaths, all in Hong Kong SAR, have been reported.

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The main symptoms of SARS as outlined by WHO

Suspect Case
A person presenting after 1 February 2003 with history of :
high fever (>38oC)
AND
one or more respiratory symptoms including cough, shortness of breath, difficulty breathing
AND one or more of the following:
close contact with a person who has been diagnosed with SARS
recent history of travel to areas reporting cases of SARS

Probable Case
A suspect case with chest x-ray findings of pneumonia or Respiratory Distress Syndrome
OR
A person with an unexplained respiratory illness resulting in death, with an autopsy examination demonstrating the pathology of Respiratory Distress Syndrome without an identifiable cause.

In addition to fever and respiratory symptoms, SARS may be associated with other symptoms including: headache, muscular stiffness, loss of appetite, malaise, confusion, rash, and diarrhea.
Early laboratory findings include low platelet and white blood cell counts. In some cases, those symptoms are followed by pneumonia in both lungs, sometimes requiring use of a respirator.

coronavirus.jpg (220x225 -- 0 bytes)
 
Coronavirus from SARS isolated in FRhK-4 cells. Thin section electron micrograph and negative stained virus particles  

Lab Diagnosis

Researchers in several countries are working towards developing fast and accurate laboratory tests for the SARS. However, until those tests have been adequately field tested and shown to be reliable, SARS diagnosis remains dependant on the clinical findings of an atypical pneumonia not attributed to another cause and a history of exposure to a suspect or probable case of SARS or their respiratory secretions and other bodily fluids. This requirement is reflected in the current WHO case definitions for suspect or probable SARS .

Status of laboratory tests currently under development

1 Antibody tests
- ELISA (Enzyme Linked ImmunoSorbant Assay) detects antibodies in the serum of SARS patients reliably as from day 21 after the onset of clinical symptoms and signs.
- Immunofluorescence Assays detect antibodies in serum of SARS patients after about day 10 of illness onset. This is a reliable test requiring the use of fixed SARS-virus, an immunofluorescence microscope and an experienced microscopist. Positive antibody tests indicate that the patient was infected with the SARS -virus.

2 Molecular tests (PCR)
PCRcan detect genetic material of the SARS -virus in various specimens (blood, stool, respiratory secretions or body tissue). Primers, which are the key pieces for a PCR test, have been made publicly available by WHO network laboratories on the WHO web site . The primers have since been used by numerous countries around the world. A ready-to-use PCR test kit containing primers and positive and negative control has been developed. Testing of the kit by network members is expected to quickly yield the data needed to assess the test?s performance, in comparison with primers developed by other WHO network laboratories. Existing PCR tests are very specific but lack sensitivity. That means that negative tests can?t rule out the presence of the SARS virus in patients. Various WHO network laboratories are working on their PCR protocols and primers to improve their reliability.

coronavirus2.jpg (220x179 -- 0 bytes)
 
  Coronavirus from SARS isolated in FRhK-4 cells. Thin section electron micrograph and negative stained virus particles

3 Cell culture
Virus in specimens (such as respiratory secretions, blood or stool) from SARS patients can also be detected by infecting cell cultures and growing the virus. Once isolated, the virus must be identified as the SARS virus with further tests. Cell culture is a very demanding test, but the only means to show the existence of a live virus.

Treatment of SARS

Currently there are no specific therapies. However, the use of physiologically targeted strategies of mechanical ventilation and intensive care unit management including fluid management and glucorticoids is the only supportive therapy available. Until more is known about the cause of these outbreaks, WHO recommends that patients with SARS be isolated with barrier nursing techniques and treated as clinically indicated. At the same time, WHO recommends that any suspect cases be reported to national health authorities.

WHO Management Guidelines

These guidelines are constantly reviewed and updated as new information becomes available. They are compiled to provide a generic basis on which national health authorities may wish to develop guidelines applicable to their own particular circumstance.

Revised 11 April 2003

Management of Suspect and Probable SARS Cases

  • Hospitalize under isolation or cohort with other suspect or probable SARS cases (see Hospital Infection Control Guidance )
  • Take samples (sputum, blood, sera, urine,) to exclude standard causes of pneumonia (including atypical causes); consider possibility of coinfection with SARS and take appropriate chest radiographs.
  • Take samples to aid clinical diagnosis SARS including:
    White blood cell count, platelet count, creatine phosphokinase, liver function tests, urea and electrolytes, C reactive protein and paired sera. (Pair sera will be invaluable in the understanding of SARS even if the patient is later not considered a SARS case)
  • At the time of admission the use of antibiotics for the treatment of community-acquired pneumonia with atypical cover is recommended
  • Pay particular attention to therapies/interventions which may cause aerolization such as the use of nebulisers with a bronchodilator, chest physiotherapy, bronchoscopy, gastroscopy, any procedure/intervention which may disrupt the respiratory tract. Take the appropriate precautions (isolation facility, gloves, goggles, mask, gown, etc. ) if you feel that patients require the intervention/therapy.
  • In SARS, numerous antibiotic therapies have been tried with no clear effect. Ribavirin with or without use of steroids has been used in an increasing number of patients. But, in the absence of clinical indicators, its effectiveness has not been proven. It has been proposed that a coordinated multicentred approach to establishing the effectiveness of ribavirin therapy and other proposed interventions be examined.

Definition of a SARS Contact

A contact is a person who may be at greater risk of developing SARS because of exposure to a suspect or probable case of SARS. Information to date suggests that risky exposures include having cared for, lived with, or having had direct contact with the respiratory secretions, body fluids and/or excretion (e.g. faeces) of a suspect or probable cases of SARS.

Management of Contacts of Probable SARS Cases

  • Give information on clinical picture, transmission, etc. of SARS to the contact
  • Place under active surveillance for 10 days and recommend voluntary home isolation
  • Ensure contact is visited or telephoned daily by a member of the public health care team
  • Record temperature daily
  • If the contact develops disease symptoms, the contact should be investigated locally at an appropriate health care facility
  • The most consistent first symptom that is likely to appear is fever

Management of Contacts of Suspect SARS Cases

As a minimum the following follow up is recommended:

  • Give information on clinical picture, transmission etc of SARS to the contact
  • Place under passive surveillance for 10 days
  • If the contact develops any symptoms, the contact should self report via the telephone to the public health authority
  • Contact is free to continue with usual activities
  • The most consistent first symptom which is likely to appear is fever

Most national health authorities may wish to consider risk assessment on an individual basis and supplement the guidelines for the management of contacts of suspected SARS cases accordingly.

Removal from Follow up

If as a result of investigations, suspected or probable cases of SARS are discarded (no longer meet suspect or probable case definitions) then contacts can be discharged from follow up.

Image Source:

Department of Microbiology,
The University of Hong Kong and the Government Virus Unit,
Department of Health,
Hong Kong SAR China

Author:

Dr. Tamer Fouad, M.D.

 

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